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Genetic Susceptibility to Distinct Bladder Cancer Subphenotypes

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dc.contributor Universitat de Vic. Escola Politècnica Superior
dc.contributor Universitat de Vic. Grup de Recerca en Bioinformàtica i Estadística Mèdica
dc.contributor.author Guey, Lin T.
dc.contributor.author García-Closas, Montserrat
dc.contributor.author Murta-Nascimento, Cristiane
dc.contributor.author Lloreta, Josep
dc.contributor.author Palencia, Laia
dc.contributor.author Kogevinas, Manolis
dc.contributor.author Rothman, Nathaniel
dc.contributor.author Vellalta, Gemma
dc.contributor.author Calle, M. Luz
dc.contributor.author Marenne, Gaëlle
dc.contributor.author Tardón, Adonina
dc.contributor.author Carrato, Alfredo
dc.contributor.author García Closas, Reina
dc.contributor.author Serra, Consol
dc.contributor.author Silverman, Debra T.
dc.contributor.author Chanock, Stephen
dc.contributor.author Real, Francisco X.
dc.contributor.author Malats i Riera, Núria
dc.date.accessioned 2014-05-26T07:54:26Z
dc.date.available 2014-05-26T07:54:26Z
dc.date.created 2010
dc.date.issued 2010
dc.identifier.citation Guey, L. T., Garcia-Closas, M., Murta-Nascimento, C., Lloreta, J., Palencia, L., Kogevinas, M., . . . EPICURO Spanish Bladder Canc Study. (2010). Genetic Susceptibility to Distinct Bladder Cancer Subphenotypes. European urology, 57(2), 283-292. doi:10.1016/j.eururo.2009.08.001 ca_ES
dc.identifier.issn 0302-2838
dc.identifier.uri http://hdl.handle.net/10854/3077
dc.description.abstract Background: Clinical, pathologic, and molecular evidence indicate that bladder cancer is heterogeneous with pathologic/molecular features that define distinct subphenotypes with different prognoses. It is conceivable that specific patterns of genetic susceptibility are associated with particular subphenotypes. Objective: To examine evidence for the contribution of germline genetic variation to bladder cancer heterogeneity. Design, setting, and participants: The Spanish Bladder Cancer/EPICURO Study is a case-control study based in 18 hospitals located in five areas in Spain. Cases were patients with a newly diagnosed, histologically confirmed, urothelial cell carcinoma of the bladder from 1998 to 2001. Case diagnoses were reviewed and uniformly classified by pathologists following the World Health Organisation/ International Society of Urological Pathology 1999 criteria. Controls were hospital- matched patients (n = 1149). Measurements: A total of 1526 candidate variants in 423 candidate genes were analysed. Three distinct subphenotypes were defined according to stage and grade: low-grade nonmuscle invasive (n = 586), high-grade nonmuscle invasive (n = 219), and muscle invasive (n = 246). The association between each variant and subphenotype was assessed by polytomous risk models adjusting for potential confounders. Heterogeneity in genetic susceptibility among subphenotypes was also tested. Results and limitations: Two established bladder cancer susceptibility genotypes, NAT2 slow-acetylation and GSTM1-null, exhibited similar associations among the subphenotypes, as did VEGF-rs25648, which was previously identified in our study. Other variants conferred risks for specific tumour subphenotypes such as PMS2-rs6463524 and CD4-rs3213427 (respective heterogeneity p values of 0.006 and 0.004), which were associated with muscle-invasive tumours (per-allele odds ratios [95% confidence interval] of 0.56 [0.41–0.77] and 0.71 [0.57–0.88], respectively) but not with non– muscle-invasive tumours. Heterogeneity p values were not robust in multiple testing according to their false-discovery rate. Conclusions: These exploratory analyses suggest that genetic susceptibility loci might be related to the molecular/pathologic diversity of bladder cancer. Validation through large-scale replication studies and the study of additional genes and single nucleotide polymorphisms are required. ca_ES
dc.format application/pdf
dc.format.extent 10 p. ca_ES
dc.language.iso eng ca_ES
dc.publisher Elsevier ca_ES
dc.rights (c) 2010 Elsevier. Published article is available at: http://dx.doi.org/10.1016/j.eururo.2009.08.001
dc.subject.other Bufeta -- Càncer -- Aspectes genètics ca_ES
dc.subject.other Polimorfisme genètic ca_ES
dc.title Genetic Susceptibility to Distinct Bladder Cancer Subphenotypes ca_ES
dc.type info:eu-repo/semantics/article ca_ES
dc.identifier.doi https://doi.org/10.1016/j.eururo.2009.08.001
dc.relation.publisherversion http://www.sciencedirect.com/science/article/pii/S0302283809008033
dc.rights.accesRights info:eu-repo/semantics/closedAccess ca_ES
dc.type.version info:eu-repo/publishedVersion ca_ES
dc.indexacio Indexat a SCOPUS
dc.indexacio Indexat a WOS/JCR ca_ES

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